Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture

Sepsis Clinical Trial

— CAESAR  

Official title:

Effect of C1-esterase Inhibitor on Systemic Inflammation in Trauma Patients With a Femur or Pelvic Fracture

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01275976
• Other study ID #: 34932
• Status: Terminated
• Phase: Phase 3
• First received: January 12, 2011
• Last updated: February 3, 2015
• Start date: April 2012
• Est. completion date: February 2015

Study information

• Verified date: February 2015
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

Trauma and major operation are associated with an excessive inflammation reaction due to tissue injury. This overwhelming immune response is considered to be a major risk factor in the pathogenesis of late inflammatory complications such as acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS) and sepsis.

The investigators hypothesize that administration of C1-esterase inhibitor (C1-INH) will attenuate the humane inflammatory response and, thereby, reduce the risk of inflammatory complications due to surgical interventions in trauma patients with a femur or pelvic fracture

Description:

Systemic inflammation in response to a femur or pelvic fracture and fixation is associated with complications, such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). The injury itself, but also the additional fixation procedure give a release of pro-inflammatory cytokines, in particular interleukin (IL)-6. This results in an aggravation of the initial systemic inflammatory response, and will cause in some patients an increased risk on the development of inflammatory complications, like ARDS and MODS. Which can lead to higher morbidity, mortality and prolonged hospital stay.

Various strategies, such as damage control orthopedics, have been proposed to prevent these complications. Another strategy is to decrease the inflammatory reaction caused by the surgical procedure, and by interventions focused on inhibition of the innate inflammatory response. This will lower the risk of complications.

A promising candidate is the endogenously produced serum protein C1-esterase inhibitor (C1-INH). This protein is an acute phase protein, produced by the liver in response to inflammatory conditions. C1-INH is a major inactivator of the complement system, but important additional anti-inflammatory properties have been demonstrated. A previous study of from our laboratory showed that administration of the drug C1-INH significantly reduced the concentration of circulating pro-inflammatory cytokines such as IL-6, during human experimental endotoxemia. Treatment with C1-INH has been proven to be safe in treatment with humans, even in high dosages and in pregnant patients with C1-INH deficiency.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Multi trauma patients

• Femur or pelvic fracture

• Injury Severity Score (ISS) = 18

• Age 18-80 yrs

Exclusion Criteria:

• Congenital C1-inhibitor deficiency

• Use of immune suppressants

• Pregnancy

• Known hypersensitivity for blood products

• Fixation of femur fracture with external fixation or osteosynthesis

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hip Fractures
• Inflammation
• Multiple Organ Dysfunction Syndrome
• Multiple Organ Failure
• Sepsis
• Trauma
• Wounds and Injuries

Intervention

Drug:
• C1-esterase inhibitor
C1-esterase inhibitor 200 U/kg infusion over 30 minutes, just before the start of the femur or pelvic fixation operation.

Other:
• Saline 0.9%
Infusion, just before the start of the femur or pelvic fixation operation

Locations

Country	Name	City	State
Netherlands	University Medical Centre Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
UMC Utrecht	Sanquin

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delta Interleukine-6		6 hours after C1-INH administration	No
Secondary	Cytokines and other markers of inflammation		up to 12 days after C1-INH administration	No
Secondary	Neutrophil redistribution and phenotype		Up to 12 days after C1-INH administration	No
Secondary	C1-inhibitor and complement concentration and activity		Up to 12 days after C1-INH administration	No
Secondary	Hemodynamic response		Up to 12 days after C1-INH administration	No